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In vitro susceptibility of 50 non-beta-lactamase-producing Neisseria gonorrhoeae strains to 12 antimicrobial agents.

The in vitro activities of six commonly used antibiotics and six newer beta-lactam agents were determined in 50 consecutive clinical isolates of beta-lactamase-negative Neisseria gonorrhoeae. The gonococci isolated were notably resistant to penicillin, ampicillin, erythromycin, and tetracycline, whereas all of the strains were susceptible to the newer beta-lactam agents cefoxitin and spectinomycin.

Anti-Bacterial Agents↗

Susceptibility of 40 Haemophilus ducreyi strains to 34 antimicrobial products.

A study was performed to examine compounds that might improve the selectivity of the primary isolation medium for Haemophilus ducreyi. The susceptibility of 40 H. ducreyi strains to 34 antimicrobial agents, including 10 antibiotics, 3 quaternary ammonium compounds, 3 phenolic derivatives, 3 acridines, and 15 heavy metal compounds, was investigated by using an agar plate dilution technique. Results were compared with the susceptibilities of other gram-negative rods which may be contaminants on isolation media. The minimal inhibitory concentration range for colistin (16 to 128 micrograms/ml) indicated that this antibiotic might be of use as a selective agent. H. ducreyi was susceptible to spectinomycin (minimal inhibitory concentration range, 16 to 64 micrograms/ml), thiamphenicol (0.12 to 1 microgram/ml), chloramphenicol (0.12 to 0.5 micrograms/ml), and streptomycin (4 to 32 micrograms/ml) and moderately susceptible to kanamycin (2 to 8 micrograms/ml). For the heavy metal compounds, a high susceptibility was seen with copper(II) chloride (2 to 8 micrograms/ml, corresponding to a concentration of 0.75 to 3 micrograms of Cu2+ ions per ml), sodium selenite (1 to 4 micrograms/ml, or 0.45 to 1.83 micrograms of Se- ions per ml), and phenylmercury acetate (0.12 to 0.5 micrograms/ml). The minimal inhibitory concentrations of quaternary ammonium compounds, acridines, and phenolic derivatives were between 1 and 32 micrograms/ml, 8 and 32 micrograms/ml, and 8 and 250 micrograms/ml, respectively.

Acridines↗

In vitro susceptibilities of Campylobacter-like organisms to twenty antimicrobial agents.

We determined MICs of 20 antimicrobial agents for 50 representative strains of four subgroups of Campylobacter-like organisms (CLOs) by agar dilution. Ampicillin, gentamicin, doxycycline, tetracycline, ceftriaxone, rifampin, spectinomycin, nalidixic acid, and chloramphenicol were active against all strains of CLOs. Most CLO strains (83%) were inhibited by 4 micrograms of sulfamethoxazole per ml and by 8 micrograms of trimethoprim-sulfamethoxazole per ml. Of type 1 strains, 28% were resistant to 8 micrograms of erythromycin per ml. In addition, cross resistance between erythromycin and clindamycin was always present. Type 1 strains exhibited a broad distribution of MICs of metronidazole and streptomycin, whereas all type 2 strains were uniformly susceptible to metronidazole and resistant to streptomycin. Unlike type 1 and 3 strains, type 2 CLOs were susceptible to cephalothin and penicillin G and highly resistant to streptomycin. The type 3 strain was uniquely resistant to cefazolin. The majority of strains were not inhibited by cefoperazone; and all were resistant to trimethoprim. In contrast to Campylobacter jejuni and Campylobacter fetus subsp. fetus, all CLOs tested were susceptible to 0.5 microgram of rifampin per ml.

Campylobacter↗

Comparative trial of single-dose ciprofloxacin and ampicillin plus probenecid for treatment of gonococcal urethritis in men.

In a double-blind comparative trial, 100 men with uncomplicated gonorrhea caused by beta-lactamase-negative Neisseria gonorrhoeae were treated with a single 0.25-g dose of ciprofloxacin administered orally or with 3.5 g of ampicillin plus 1.0 g of probenecid administered orally. Urethral infection was eradicated in all 49 men treated with ciprofloxacin and in 47 (92%) of 51 men treated with ampicillin-probenecid (P = 0.12). The geometric mean MICs for pretreatment isolates were 0.008 microgram of ciprofloxacin per ml, 0.09 microgram of penicillin G per ml, 0.52 microgram of tetracycline per ml, and 23.5 micrograms of spectinomycin per ml. Chlamydia trachomatis infection persisted in 10 of 11 men treated with ciprofloxacin and in 11 of 14 men treated with ampicillin-probenecid. A single 0.25-g dose of ciprofloxacin was effective for treatment of uncomplicated urethral gonorrhea in men, but it did not eradicate coinfection with C. trachomatis.

Adolescent↗

Membrane perturbation by aminoglycosides as a simple screen of their toxicity.

A simple test to assess the toxicity of aminoglycosides was designed based on the interaction of these drugs with phosphatidylinositol bisphosphate. The fluorescent probe 1-anilino-8-naphthalene sulfonate was incorporated into liposomes composed of L-alpha-phosphatidylcholine and phosphatidylinositol bisphosphate (4:1 molar ratio), and changes in fluorescence induced by the aminoglycosides were measured. The magnitude of these changes correlated well with the intrinsic ototoxicity of the drugs previously established in cochlear perfusions: neomycin greater than gentamicin approximately equal to tobramycin greater than amikacin approximately equal to kanamycin approximately equal to netilmicin greater than neamine approximately equal to spectinomycin. Correlations were not accurate when other phospholipids were substituted for phosphatidylinositol bisphosphate. An alternative in vitro test, measurement of the zeta potential of liposomes, ranked the drugs according to their electrostatic charge but not their toxicity. These results suggest that: a simple screen for aminoglycoside toxicity can be established and perturbation of membranes containing phosphatidylinositol bisphosphate is a key step in aminoglycoside ototoxicity.

Aminoglycosides↗

Cationic antitrypanosomal and other antimicrobial agents in the therapy of experimental Pneumocystis carinii pneumonia.

Cationic compounds used in the treatment of veterinary African trypanosomiasis have structural properties similar to those of pentamidine, which has been used in the therapy of human trypanosomiasis and infection with Pneumocystis carinii. We have compared the activities of these drugs and other antimicrobial agents in an immunosuppressed rat model of P. carinii pneumonia. Diminazene, imidocarb, amicarbalide, quinapyramine, and isometamidium showed efficacy greater than or equal to that of pentamidine in the therapy of P. carinii infection, whereas ethidium and methylglyoxal bis(guanylhydrazone) were only slightly active against the organism. Diminazene and pentamidine also exhibited comparable efficacy in P. carinii prophylaxis, alpha-Difluoromethylornithine (DFMO), a polyamine inhibitor, was ineffective therapy when used alone and did not improve the effectiveness of pentamidine or diminazene. Quinine, quinidine, quinacrine, chlorpromazine, spiramycin, Pentostam, Astiban, dehydroemetine, ampicillin, gentamicin, chloramphenicol, and spectinomycin also showed little or no activity against the organism. Thus, in this model anti-P. carinii activity appears to be a common property of veterinary cationic trypanocidal compounds. This should be important in studying structure-activity relationships and in developing new drugs for the treatment of P. carinii infection in humans.

Amidines↗

Antimicrobial susceptibilities of southern African isolates of Haemophilus ducreyi.

We determined the antimicrobial susceptibilities of 122 recent clinical isolates of Haemophilus ducreyi to 24 antimicrobial agents. All isolates produced beta-lactamase and were resistant to penicillins. The majority of strains were also resistant to tetracycline, doxycycline, and sulfamethoxazole. All isolates were susceptible to macrolides, quinolones, extended-spectrum cephalosporins, spectinomycin, rifampin, and amoxycillin-clavulanate. Reduced susceptibility to minocycline, co-trimoxazole, and kanamycin was noted. Chloramphenicol and thiamphenicol resistance was noted for the first time among southern African strains.

Anti-Bacterial Agents↗

The dhfrI trimethoprim resistance gene of Tn7 can be found at specific sites in other genetic surroundings.

The dhfrI gene, mediating high-level trimethoprim resistance, was earlier found only on Tn7. Evidence is given here for an alternative location of this gene at a site identical to sites observed earlier for dhfrII on plasmid R388, dhfrV on pLMO20, and aadA on Tn21. All these genes and dhfrI are precisely inserted as discrete GTTA-flanked elements at distinct loci in very conserved surrounding sequences. One of these dhfrI insertions was observed to occur in association with a similarly inserted aadA nucleotidyltransferase gene, which mediates streptomycin and spectinomycin resistance. Close to the insertion site, there is an open reading frame translating into a 337-amino-acid peptide which shows striking similarities to recombinases of the integrase family, sulI, the sulfonamide resistance gene, is very often found close to the insertion point forming a genetic surrounding, originally observed as a part of Tn21-like transposons. The alleged integration mechanism thus provides a recombination pathway for the genetic linkage of sulfonamide and other antibiotic resistance genes, including the most frequently encountered gene for trimethoprim resistance, dhfrI. Furthermore, the newly observed location of dhfrI could shed light on the evolution of the antibiotic resistance region of Tn7, which could be able to take up genes by the same mechanism as that of Tn21-like transposons.

Base Sequence↗

Oral ciprofloxacin versus ceftriaxone for the treatment of urethritis from resistant Neisseria gonorrhoeae in Zambia.

Neisseria gonorrhoeae strains resistant to treatment with penicillin, tetracycline, and/or spectinomycin are increasing in prevalence in many parts of the world. In Zambia, 52% of N. gonorrhoeae isolates produced beta-lactamase in 1986. Few oral regimens have proven effective for treatment of resistant N. gonorrhoeae. We conducted a prospective, double-blind, randomized clinical trial of 250 mg of ciprofloxacin given orally versus 250 mg of ceftriaxone given intramuscularly for treatment of uncomplicated gonococcal urethritis in adult males. Two hundred men were enrolled and treated. The two groups were comparable in age (27.5 years), prevalence of latent syphilis (14 and 10%), and human immunodeficiency virus infection (32 and 38%). Of 165 patients with cultures positive for N. gonorrhoeae who returned for follow-up, ciprofloxacin cured 83 of 83 (100%), including 26 with penicillinase-producing N. gonorrhoeae (PPNG) and 21 with N. gonorrhoeae with chromosomally mediated resistance to multiple antibiotics (CMRNG), and ceftriaxone cured 81 of 82 (98.7%), including 30 with PPNG and 19 with CMRNG. Both treatment regimens were well tolerated. Chlamydia trachomatis in urethral exudate was found by direct fluorescent-antibody microscopic examination or by culture in 10 (5%) participants. All N. gonorrhoeae isolates were inhibited by ceftriaxone at 0.06 micrograms/ml, except one which was inhibited at 0.125 micrograms/ml, while ciprofloxacin inhibited all isolates at 0.03 micrograms/ml. Ciprofloxacin is a safe and effective therapy for uncomplicated gonococcal urethritis, including that caused by PPNG and CMRNG in human immunodeficiency virus-infected men.

Adult↗

Comparison of in vitro antimicrobial susceptibilities of Mycobacterium avium-M. intracellulare strains from patients with acquired immunodeficiency syndrome (AIDS), patients without AIDS, and animal sources.

Difloxacin, A-56620, cefazolin, cefotaxime, ceftizoxime, cephapirin, SK&F 88070, and spectinomycin were used to compare the in vitro susceptibilities of Mycobacterium avium-M. intracellular isolates from patients with acquired immunodeficiency syndrome (AIDS), patients without AIDS, and diseased animals. Against the isolates from humans without AIDS, the quinolone compounds difloxacin and A-56620 were found to be the most effective, each inhibiting 50% of strains at a concentration of 2 micrograms/ml. The remaining antimicrobial agents had MICs for 50% of strains tested of at least 32 micrograms/ml. Statistically significant differences were observed in the antibiogram patterns among the M. avium-M. intracellulare strains from each of the three sources.

Acquired Immunodeficiency Syndrome↗

In vitro antibacterial activities of PD 131628, a new 1,8-naphthyridine anti-infective agent.

PD 131628 is a new aminopyrrolidine-substituted fluorocyclopropyl naphthyridine quinolone which possesses high in vitro activity against a wide spectrum of bacterial species. The MICs for greater than or equal to 90% of strains were 0.125 to 0.25 microgram/ml for staphylococci, Streptococcus pyogenes, and S. pneumoniae; 0.5 micrograms/ml for S. agalactiae and Enterococcus faecalis; 0.125 micrograms/ml for members of the family Enterobacteriaceae and Acinetobacter spp.; 0.5 micrograms/ml for Pseudomonas aeruginosa; and less than or equal to 0.03 micrograms/ml for Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Neisseria gonorrhoeae. In these in vitro comparisons with ciprofloxacin, PD 131628 is more active against gram-positive organisms, approximately equivalent against gram-negative organisms, and, like most other quinolones, relatively inactive against gram-negative anaerobes. In most instances, the in vitro potency of PD 131628 exceeded those of widely used compounds: ciprofloxacin, imipenem, ampicillin, penicillin G, oxacillin, cefazolin, ceftazidime, cefoxitin, cefsulodin, aztreonam, piperacillin, amikacin, spectinomycin, doxycycline, erythromycin, metronidazole, and vancomycin.

Anti-Bacterial Agents↗

Comparison of methods for in vitro testing of susceptibility of porcine Mycoplasma species to antimicrobial agents.

The MICs of 18 antimicrobial agents used against strains of three porcine Mycoplasma species were determined by a serial broth dilution method. Twenty field strains of M. hyorhinis, ten field strains of M. hyopneumoniae, six field strains of M. flocculare, and the type strains of these species were tested. Twelve field strains and the type strain of M. hyorhinis were also tested by an agar dilution method. Tests were read at various time points. When the broth dilution method was used, the final MIC had to be read 2 days after color changes had stopped. MICs of tetracycline, oxytetracycline, doxycycline, and minocycline were low for the three Mycoplasma species tested. MICs of chlortetracycline were 8 to 16 times higher than MICs of the other tetracyclines. Spiramycin, tylosin, kitasamycin, spectinomycin, tiamulin, lincomycin, and clindamycin were effective against all strains of M. hyorhinis and M. hyopneumoniae. The quinolones were highly effective against M. hyopneumoniae but less effective against M. hyorhinis. The susceptibility patterns for M. hyopneumoniae and M. flocculare were similar.

Animals↗

Molecular characterization of the class II multiresistance transposable element Tn1403 from Pseudomonas aeruginosa.

Transposon Tn1403 is a 19.9-kb multiresistance class II transposable element originally found on the RPL11 plasmid from a clinical isolate of Pseudomonas aeruginosa. It encodes resistance to ampicillin (PSE-1 beta-lactamase), streptomycin and spectinomycin (aadA and aphC), and chloramphenicol (cat). It has structural homology with the tnpM and tnpI sequences of Tn21 and inverted repeats and res and tnpR sequences of Tn501, but it has no structural homology nor functional complementation with the resolvase gene of Tn21 or Tn3. Sequence analysis revealed long inverted repeats at each extremity of Tn1403 containing 38-bp inverted repeats that were 97.4% similar to those of Tn1721 and 5-bp direct repeats. Transposition assays showed a low frequency of transposition (3.5 x 10(-6)) compared with that of Tn3 (3.3 x 10(-3)) and no resolution of cointegrates.

Base Sequence↗

Physical mapping of the mec region of an American methicillin-resistant Staphylococcus aureus strain.

We mapped part of the mec region of a locally prevalent strain of Staphylococcus aureus. The mec region was found to harbor an insert of the transposon Tn554, which encodes spectinomycin and macrolide-lincosamide-streptogramin B resistance, and a 4.6-kb segment of DNA that contains the kanamycin resistance gene aadD. This 4.6-kb segment appears to be an integrated form of a previously described plasmid, pUB110, and is flanked by copies of the insertion sequence IS257. The integration event may be an example of processes that have led to accretion of resistance determinants in the mec region of S. aureus.

Base Sequence↗

In vitro antibiotic susceptibilities of Neisseria gonorrhoeae isolates in the Philippines.

Antibiotic susceptibility surveillance testing was performed on clinical isolates of Neisseria gonorrhoeae collected in September 1989 in the Philippines. beta-Lactamase was produced by 77 (55%) of 140 isolates. In vitro MIC testing revealed significant resistance to penicillin (MIC for 90% of isolates [MIC90], greater than 64 micrograms/ml), tetracycline (MIC90, 4 micrograms/ml), and cefmetazole (MIC90, 8 micrograms/ml). Spectinomycin resistance was rare (10 of 117), but the MIC90 was 32 micrograms/ml. Isolates were susceptible to fluoroquinolones and cephalosporins at the time of this survey, as evidenced by the MIC90s of ciprofloxacin (0.25 microgram/ml), norfloxacin (2.0 micrograms/ml), ofloxacin (0.625 microgram/ml), cefpodoxime (2.0 micrograms/ml), cefotaxime (1.0 microgram/ml), ceftazidime (0.25 microgram/ml), ceftizoxime (0.25 microgram/ml), and ceftriaxone (0.06 microgram/ml). To date, ceftriaxone resistance has not emerged, despite the widespread use of this antibiotic in the Philippines.

Anti-Bacterial Agents↗

Susceptibilities of Mycoplasma bovis, Mycoplasma dispar, and Ureaplasma diversum strains to antimicrobial agents in vitro.

The purpose of this study was to determine the susceptibility of various strains of Mycoplasma bovis, Mycoplasma dispar, and Ureaplasma diversum, which are prevalent causes of pneumonia in calves, to 16 antimicrobial agents in vitro. The MICs of the antimicrobial agents were determined by a serial broth dilution method for 16 field strains and the type strain of M. bovis, for 19 field strains and the type strain of M. dispar, and for 17 field strains of U. diversum. Final MICs for M. bovis and M. dispar were read after 7 days and final MICs for U. diversum after 1 to 2 days. All strains tested were susceptible to tylosin, kitasamycin, and tiamulin but were resistant to nifuroquine and streptomycin. Most strains of U. diversum were intermediately susceptible to oxytetracycline but fully susceptible to chlortetracycline; most strains of M. bovis and M. dispar, however, were resistant to both agents. Strains of M. dispar and U. diversum were susceptible to doxycycline and minocycline, but strains of M. bovis were only intermediately susceptible. Susceptibility or resistance to chloramphenicol, spiramycin, spectinomycin, lincomycin, or enrofloxacin depended on the species but was not equal for the three species. The type strains of M. bovis and M. dispar were more susceptible to various antimicrobial agents, including tetracyclines, than the field strains. This finding might indicate that M. bovis and M. dispar strains are becoming resistant to these agents. Antimicrobial agents that are effective in vitro against all three mycoplasma species can be considered for treating mycoplasma infections in pneumonic calves. Therefore, tylosin, kitasamycin, and tiamulin may be preferred over oxytetracycline and chlortetracycline.

Animals↗

In vitro antimicrobial susceptibilities of Nocardia species.

The in vitro activities of various quinolones, two new aminoglycosides, a new cephamycin analog (cefmetazole) and a new spectinomycin analog (trospectomycin), imipenem, and trimethoprim-sulfamethoxazole against 26 isolates of Nocardia asteroides, 7 isolates of N. brasiliensis, and 6 isolates of N. caviae were determined by a broth microdilution method. The three new quinolones, PD 117558, PD 117596 and PD 112739, inhibited 90% of N. asteroides at 1 to 2 micrograms/ml, and two new aminoglycosides, SCH 21420 and SCH 22591, inhibited 90% of N. asteroides at 2 to 4 micrograms/ml. Among the beta-lactams, cefmetazole was more active than imipenem. N. brasiliensis and N. caviae isolates were also very susceptible to the three quinolones (MICs for 50% of the isolates, 0.25 to 1 microgram/ml) and the two aminoglycosides (MICs for 50% of the isolates, 1 to 2 micrograms/ml). Cefmetazole was moderately active against N. brasiliensis, whereas imipenem showed poor activity against both of these species.

4-Quinolones↗